A study to learn about the safety and effectiveness of CRN04894 on participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Crinetics Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

22 Jul 2025 → ongoing

Decision date (initial)

2025-03-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Crinetics Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

Safety Objectives
To evaluate the safety and tolerability of atumelnant
Primary Efficacy Objective
To evaluate efficacy of atumelnant, measured by change from baseline in serum androstenedione (A4)

Secondary objectives 1

1. Secondary Efficacy Objectives: To evaluate efficacy of atumelnant, measured by change from baseline in serum 17-hydroxyprogesterone (17-OHP) To evaluate the efficacy of atumelnant, as assessed by GC need

Conditions and MedDRA coding

CONGENITAL ADRENAL HYPERPLASIA

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Participants with CAH who have completed the Treatment Period in a Crinetics parent atumelnant CAH study and in the opinion of the Investigator had an acceptable benefit-risk assessment in the completed study and would benefit from continued dosing in this extension study: a. Group 1: Participants meeting the above criteria and did not have study drug administration interrupted between EOT of the parent study and the commencement of the OLE study. b. Group 2: Participants meeting the above criteria but had study drug administration interrupted between EOT of the parent study and the commencement of the OLE study. Note: The maximum dose of atumelnant in this study is 120 mg QD.
2. 2. Female participants who engage in heterosexual intercourse must: a. Be of nonchildbearing potential, defined as either surgically sterile (ie, hysterectomy or bilateral salpingectomy for at least 3 months, or bilateral oophorectomy), OR b. Be postmenopausal with at least 1 year of amenorrhea. In participants with less than 1 year of amenorrhea, confirmation is required with 2 follicle-stimulating hormone (FSH) measurements. A documented, historical test result measured prior to Screening may be used as 1 of the 2 measurements. The FSH value should be ≥30 IU/L to confirm menopausal status, OR c. Agree to use a highly effective method of contraception from the beginning of Screening until at least 2 weeks after the last dose of study drug. Contraceptive use by men and women also should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Periodic abstinence (ie, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Note: For further information about contraception, see Section 11.3 for details.
3. 3. Male participants agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 2 weeks after the last dose of study drug (or be surgically sterile [ie, vasectomy with a confirmed absence of sperm in ejaculate]; or agree to remain abstinent on a long-term and persistent basis). Male participants should also agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug. Note: For further information about contraception, see Section 11.3 for details.
4. 4. Participants are willing and able to give signed informed consent, including compliance with the requirements and restrictions listed in the Informed Consent Form (ICF).
5. 5. Participants are willing and able to comply with the study procedures as specified in the protocol and comply with the study treatment.

Exclusion criteria 15

1. The following exclusion criteria apply to all participants (Group 1 and Group 2): 1. Any medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the participant’s safety or ability to complete the study.
2. 2. Participants have known history of (that is within the past 12 months), or current alcohol or drug abuse.
3. 3. Participants have any mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor compliance with medical instructions.
4. 4. Participants have a known allergy or hypersensitivity to any of the test materials or related compounds, including being at high risk of adrenal insufficiency as judged by the Investigator.
5. 5. Women who are pregnant or lactating or, if of childbearing potential, who are unwilling to use highly effective contraception as described in this study. Male participants who are unwilling to use highly effective contraception as described in this study.
6. 6. Participant is an employee or immediate family member of an employee of Crinetics.
7. 7. Participants who have been dosed with an investigational drug (other than atumelnant) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to informed consent or plan to use an investigational drug in another study.
8. 8. Participants who have had an active malignant disease within the last 5 years prior to Screening excluding dermal squamous or basal cell carcinoma of the skin with complete local excision or resected cervical carcinoma in situ.
9. 9. Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
10. The following additional exclusion criteria apply to participants in Group 2 only (Screening required): 10. Participants with any clinically significant abnormal laboratory test during Screening or clinically significant concomitant disease other than CAH including but not limited to cardiovascular disease; moderate or severe renal insufficiency (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2 using Chronic Kidney Epidemiology Collaboration [CKD-EPI] formula) at Screening; or Significant liver disease or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3× upper limit of normal (ULN), and/or total bilirubin >1.5×ULN during Screening. Participants with previously diagnosed Gilbert’s syndrome not accompanied by other hepatobiliary disorders and associated with total bilirubin <3.5 mg/dL (<51.3 μmol/L) will be permitted.
11. 11. Participants with a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic GC therapy.
12. 12. Participants with a history of major surgery/surgical therapy for any cause within 4 weeks prior to Screening.
13. 13. Participants with poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5% (≥69 mmol/mL).
14. 14. Participants with hypothyroidism who are not receiving adequate hormone replacement therapy based on thyroid hormone levels measured at the time of Screening, as determined by the Investigator.
15. 15. Participant has an average (of 3 electrocardiograms [ECGs]) Fridericia’s corrected QT (QTcF) interval >450 milliseconds (msec) (men) or >470 msec (women), time interval between P and R waves (PR interval) >220 msec, time interval of the QRS complex (QRS) interval >120 msec, second- or third-degree atrioventricular block, left bundle branch block, or hemiblock at Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety Endpoints: Incidence of treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (SAEs), adverse events of special interest (AESI [adrenal insufficiency]) and any adverse events (AEs) leading to discontinuation Incidence of glucocorticoid (GC) deficiency/adrenal insufficiency and adrenal crisis Incidence of hospitalizations related to congenital adrenal hyperplasia (CAH) Efficacy Endpoint: Change from baseline in morning serum A4 over time

Secondary endpoints 1

1. Secondary Efficacy Endpoints Change from baseline in morning (before 11:00 AM) serum 17-OHP over time Change from baseline in daily GC dose (hydrocortisone [HC] mg equivalents body surface area [BSA] adjusted) over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Crinetics Pharmaceuticals Inc.

Sponsor organisation

Crinetics Pharmaceuticals Inc.

Address

6055 Lusk Boulevard

City

San Diego

Postcode

92121-2700

Country

United States

Scientific contact point

Organisation

Crinetics Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Crinetics Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Third parties 13

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications